Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study |
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Authors: | Adriana G. Guimarã es,Luciana Scotti,Marcus Tullius Scotti,Francisco J.B. Mendonç a Jú nior,Nayara S.R. Melo,Rafael S. Alves,Waldecy De Lucca Jú nior,Daniel P. Bezerra,Daniel P. Gelain,Lucindo J. Quintans Jú nior |
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Affiliation: | 1. Department of Health Education, Federal University of Sergipe, Lagarto, SE, Brazil;2. Federal University of Paraíba, João Pessoa, PB, Brazil;3. State University of Paraiba, Biological Science Department, Laboratory of Synthesis and Drug Delivery, 58070-450 João Pessoa, PB, Brazil;4. Department of Physiology, Federal University of Sergipe, SãoCristóvão, SE, Brazil;5. Department of Morphology, Federal University of Sergipe, SãoCristóvão, SE, Brazil;6. Oswaldo Cruz Foundation, Laboratory of Tissue Engineering and Immunopharmacology, Salvador, BA, Brazil;g Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil |
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Abstract: | AimsThe present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice.Main methodsCarvacrol treatment (12.5–50 mg/kg s.c.) once daily for 15 days was started 24 h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABAA receptors.Key findingsCARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABAA.SignificanceTogether, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain. |
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Keywords: | Carvacrol (PubChem CID: 10364) Morphine (PubChem CID: 5288826) |
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